Targeting endothelin-1 receptor/beta-arrestin1 network for the treatment of ovarian cancer

Areas covered: In this article, we discuss the role of the signaling network between ET-1R and key pathways mediated by the scaffold protein beta-arr1, as part of signaling complex, or as a transcription coactivator, promoting precise control of transcription of different genes, including ET-1. Therefore ET-1R/beta-arr1 is an actionable node involved in the activation of a persistent feedback loop that contributes to bypass signaling. Targeting ET-1R empowering this circuit can represent a necessary measure to reach clinical efficacy. Preclinical studies demonstrate that blocking ET-1R by FDA approved dual ETAR/ETBR antagonist prevents beta-arr1 network formation, offering a novel therapeutic strategy in ovarian cancer patients.

Introduction: Endothelin-1 receptor (ET-1R)/beta-arrestin1 (beta-arr1) signaling is dysregulated in ovarian cancer. This signaling circuit enables cancer cells to engage several signaling and transcriptional networks that are pervasively intertwined, and represent a potential therapeutic target for developing novel agents for ovarian cancer treatment.